Qing-Zhi-Tiao-Gan-Tang (QZTGT) prevents nonalcoholic steatohepatitis (NASH) by expression pattern correction

Hang Chu; Weitao Zhang; Yan Tan; Zhipeng Diao; Peng Li; Yapeng Wu; Like Xie; Jianguo Sun; Ke Yang; Pingping Li; Cen Xie; Ping Li; Qian Hua; Xiaojun Xu

doi:10.1016/j.jep.2023.116665

Qing-Zhi-Tiao-Gan-Tang (QZTGT) prevents nonalcoholic steatohepatitis (NASH) by expression pattern correction

J Ethnopharmacol. 2023 Dec 5:317:116665. doi: 10.1016/j.jep.2023.116665. Epub 2023 Jun 4.

Authors

Hang Chu¹, Weitao Zhang¹, Yan Tan², Zhipeng Diao¹, Peng Li², Yapeng Wu¹, Like Xie¹, Jianguo Sun¹, Ke Yang², Pingping Li³, Cen Xie⁴, Ping Li¹, Qian Hua⁵, Xiaojun Xu⁶

Affiliations

¹ State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, Nanjing, Jiangsu, China.
² School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China.
³ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, 100050, China.
⁴ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
⁵ School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: huaq@bucm.edu.cn.
⁶ State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, Nanjing, Jiangsu, China. Electronic address: xiaojunxu2000@163.com.

PMID: 37279813
DOI: 10.1016/j.jep.2023.116665

Abstract

Ethnopharmacological relevance: Qing-Zhi-Tiao-Gan-Tang or Qing-Zhi-Tiao-Gan Decoction (QZTGT) is based on the compatibility theory of traditional Chinese medicine (TCM), that is a combination of three classical formulae for the treatment of nonalcoholic fatty liver disease (NAFLD). Its pharmacodynamic material basis is made up of quinones, flavanones, and terpenoids.

Aim of the study: This study aimed to look for a promising recipe for treating nonalcoholic steatohepatitis (NASH), a more advanced form of NAFLD, and to use a transcriptome-based multi-scale network pharmacological platform (TMNP) to find its therapy targets.

Materials and methods: A classical dietary model of NASH was established using MCD (Methionine- and choline-deficient) diet-fed mice. Liver coefficients like ALT, AST, serum TC, and TG levels were tested following QZTGT administration. A transcriptome-based multi-scale network pharmacological platform (TMNP) was used to further analyze the liver gene expression profile.

Results: The composition of QZTGT was analyzed by HPLC-Q-TOF/MS, a total of 89 compounds were separated and detected and 31 of them were found in rat plasma. QZTGT improved liver morphology, inflammation and fibrosis in a classical NASH model. Transcriptomic analysis of liver samples from NASH animal model revealed that QZTGT was able to correct gene expression. We used transcriptome-based multi-scale network pharmacological platform (TMNP) to predicted molecular pathways regulated by QZTGT to improve NASH. Further validation indicated that "fatty acid degradation", "bile secretion" and "steroid biosynthesis" pathways were involved in the improvement of NASH phenotype by QZTGT.

Conclusions: Using HPLC-Q-TOF/MS, the compound composition of QZTGT, a Traditional Chinese prescription, was separated, analyzed and identified systematically. QZTGT mitigated NASH symptoms in a classical dietary model of NASH. Transcriptomic and network pharmacology analysis predicted the potential QZTGT regulated pathways. These pathways could be used as therapeutic targets for NASH.

Keywords: Fibrosis; Inflammation; Lipogenesis; NASH; QZTGT; TMNP.

MeSH terms

Animals
Choline
Diet
Disease Models, Animal
Liver / metabolism
Liver Cirrhosis / drug therapy
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease* / drug therapy
Non-alcoholic Fatty Liver Disease* / genetics
Non-alcoholic Fatty Liver Disease* / metabolism
Rats

Substances

Choline